Omega-Conotoxins derived from a variety of Conus species will be used as biological probes to explore the role of voltage-sensitive Ca channels in the mammalian central nervous system. The unusual specificity of omega-conotoxins for calcium channel subtypes and their capacity for biochemical manipulation will be exploited in an examination of calcium channel diversity. The work will focus on the use of a newly discovered peptide from Conus magus, MVIIC, which identifies and defines calcium channel subtypes beyond those targeted by any other known ligand. MVIIC receptor targets will be characterized in competition binding, autoradiographic, and photoaffinity crosslinking studies. One target of the MVIIC peptide is cerebellar "P" channel subtypes and a comparison with this toxin and the "P" channel defining ligand omega-agatoxin IVA will be made. In addition, the subset of non-"L", non-"N" voltage sensitive calcium channels which modulate neurotransmitter release will be investigated. These studies will attempt to define subunit composition, ligand binding sites, and the modulation of expressed channels.